Abstract 5531: Loss of csf2(gm-csf) with cisplatin treatment decreases metastasis and improves survival in a hpv positive head and neck cancer murine model

Abstract

Abstract Granulocyte macrophages colony stimulating factor (GM-CSF) also known as CSF2 is a popular cytokine responsible for homeostasis. According to TCGA databank CSF2 expression upregulated in human HPV+ (Human Papilloma Virus) Head and Neck Small Cell Carcinoma (HNSCC) compared to normal tissue. The mechanism of CSF2 in tumor progression and chemo resistance has not been well studied. Previously, our lab generated a murine model of HPV+ HNSCC that is partially responsive to cisplatin and radiation (like human disease). The role of our study is to evaluate the importance of Csf2 with cisplatin treatment (CT) in HPV + HNSCC in the murine model. Using CRISPR-Cas9 technology we knocked out the expression of the Csf2 ligand in our parental mEERL (murine E6 E7 Ras Luciferase) tumor cell line and implanted both the parental mEERL tumor and the Csf2 KO mEERL tumor in the oral cavity of C57BL6/J mice. When tumors reached a palpable size, we administered Cisplatin (20mg/m2, 3 doses total). We observed slow tumor growth in absence of Csf2 without treatment. On the other hand, we observed tumor regression in both tumor models with cisplatin treatment. Post treatment, mice with Csf2 KO tumors had a significantly prolonged rate of survival. To evaluate the role of Csf2 in the Tumor Microenvironment (TME), we collected the tumors 96 hours post CT and characterized the TME using multicolored flow cytometry. The results showed that post treatment mice with Csf2 KO tumors increased the number of the Natural Killer cell population and a surge of M-MDSC (Ly6Chi) population. The synergistic effect of knocking out Csf2 and cisplatin treatment in our tumor model appears to be driven by chemokine and cytokine changes in the TME. Simultaneously, we observed significantly lower levels of lung metastasis in Csf2 KO tumor bearing mice compared to those with parental mEERL tumors. Whereas we have seen increased metastasis in ipsilateral lymph node of Csf2 KO mice. This metastasis data mimics human disease where many patients have regional lymph node involvement, but few develop distant metastasis. These results indicate that GM-CSF (CSF2) in the TME could be an excellent target that would cause less metastasis and improved overall survival. Further investigations are needed to understand the underlying mechanism of immune response in the absence of CSF2 in the TME. Citation Format: Payal Ghosh, Craig Welbon, William C. Spanos. Loss of csf2(gm-csf) with cisplatin treatment decreases metastasis and improves survival in a hpv positive head and neck cancer murine model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5531.